It is well recognized that Salmonella can survive long-term starvation and desiccation stresses and contaminate foods that have intermediate to low water activities; however, little is known about the specific molecular mechanisms underlying its survival and persistence in low water activity foods. In this study, we used the RNA-seq approach to compare the transcriptomes (27-33 million 36-bp reads per sample) of a Salmonella enterica subsp. enteric serovar Enteritidis strain ATCC BAA-1045 after inoculation in peanut oil (water activity 0.30) for 72 h, 216 h and 528 h to those grown in Luria-Bertani (LB) broth for 12 h and 312 h. Our results showed that desiccated Salmonella cells in peanut oil were in a physiologically dormant state with <5% of its genome being transcribed compared to 78% in LB broth. Among the few detected transcripts in peanut oil, genes involved in heat and cold shock response, DNA protection and regulatory functions likely play roles in cross protecting Salmonella from desiccation and starvation stresses. In addition, non-coding RNAs may also play roles in Salmonella desiccation stress response. This is the first report of using RNA-seq technology in characterizing bacterial transcriptomes in a food matrix.